Immunoheterogeneity of parathyroid hormone in venous effluent serum from hyperfunctioning parathyroid glands.

Immunoheterogeneity of parathyroid hormone in venous effluent serum from hyperfunctioning parathyroid glands.
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功能亢进的甲状旁腺静脉流出血清中甲状旁腺激素的免疫异质性。

DOI:
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发表时间:
1977
影响因子:
15.9
通讯作者:
C. Arnaud
C. Arnaud
中科院分区:
医学1区
文献类型:
--
作者:
J. Flueck;F. P. D. Bella;A. Edis;Jean M. Kehrwald;C. Arnaud

文献摘要

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甲状旁腺功能亢进者血浆中的免疫反应性甲状旁腺激素(iPTH)主要由该激素的羧基(COOH)末端片段组成。尽管这些片段被认为主要或仅由甲状旁腺分泌的完整人 PTH {hPTH(1-84)} 的外周代谢产生,但对于体内 iPTH 片段的来源存在分歧。为了重新审视这个问题,我们使用高分辨率凝胶过滤系统(逆流运行的 Bio-Gel P-150 柱)分离了​​四名原发性甲状旁腺功能亢进症患者的外周血和甲状腺或甲状旁腺静脉流出血清。使用两种 PTH 放射免疫测定法分析柱流出物,一种针对分子的氨基 (NH(2)) 末端区域,另一种针对 COOH 末端区域。在研究的所有四种甲状腺或甲状旁腺静脉流出血清中,iPTH 比同一患者的外周血清高 9-180 倍;分级后,hPTH(1-84) 仅占总 iPTH 的一部分(针对 hPTH COOH 末端区域的测定为 35-55%,针对 NH(2) 末端区域的测定>90%。)在 hPTH(1-84) 后,剩余的 iPTH 作为 NH(2) 或 COOH 末端 hPTH 片段从 Bio-Gel P-150 中洗脱。这些结果表明甲状旁腺肿瘤分泌大量的 hPTH 片段。根据对血清中摩尔浓度的估计,如果肿瘤分泌的 COOH 末端 hPTH 片段的存活时间(如其他几位工作人员估计的那样)是 hPTH(1-84) 的 5-10 倍,那么它们可以解释外周血清中的大部分肽。我们的结论是,与已发表的信息相反,功能亢进的甲状旁腺组织的分泌产物可能是血清 PTH 免疫异质性的主要来源。
The immunoreactive parathyroid hormone (iPTH) in the plasma of hyperparathyroid man consists largely of carboxyl (COOH)-terminal fragments of the hormone. Although these fragments have been thought to arise principally or solely from peripheral metabolism of intact human PTH {hPTH(1-84)} secreted from the parathyroid gland, there is disagreement about the source of iPTH fragments in vivo. To reexamine this question, we fractionated peripheral and thyroid or parathyroid venous effluent sera from four patients with primary hyperparathyroidism using a high-resolution gel filtration system (Bio-Gel P-150 columns run by reverse flow). The column effluents were analyzed using two PTH radioimmunoassays, one directed toward the amino(NH(2))-terminal region of the molecule, the other toward the COOH-terminal region. In all four thyroid or parathyroid venous effluent sera studied, iPTH was 9-180 times higher than in peripheral serum from the same patient; after fractionation, hPTH(1-84) accounted for only a portion of the total iPTH (35-55% with the assay directed toward the COOH-terminal region of hPTH, >90% with the NH(2)-terminal directed assay.) The remaining iPTH eluted from Bio-Gel P-150 after hPTH(1-84) as NH(2)-or COOH-terminal hPTH fragments. These results suggest that parathyroid tumors secrete large quantities of hPTH fragments. Based on estimates of their molar concentrations in serum, tumor-secreted COOH-terminal hPTH fragments could account for most of these peptides in peripheral serum if their survival times were, as estimated by several other workers, 5-10 times that of hPTH(1-84). We conclude that, in contrast to published information, secretory products of hyperfunctioning parathyroid tissue are probably a major source of serum PTH immunoheterogeneity.